Our People

Biosketch

Dr. Sharon Glynn graduated with a BSc in Biotechnology from Dublin City University in 1997. Following her graduation with her B.Sc in Biotechnology, Dr. Glynn began research toward her PhD, based in the National Cell and Tissue Culture Centre in Dublin City University, under the supervision of Prof. Martin Clynes.  She graduated in 2003, with her PhD thesis entitled ??An investigation of the role of the ErbB receptor family in chemotherapeutic drug resistance and invasion in human breast cancer?.  After graduation Dr. Glynn served as a research officer at the National Institute for Cellular Biotechnology in Dublin City University where she studied the efficacy of new therapeutics including cholesterol lowering statins on breast cancer and melanoma proliferation and invasion. In 2003 Dr. Glynn received a travel award from Health Research Board of Ireland to attend the Principles and Practices of Cancer Prevention and Control Diploma course, at NCI, Bethesda, Maryland, USA. This led to her applying to the NCI Cancer Prevention Fellowship Program.  Dr. Glynn was subsequently sponsored by the All-Ireland NCI Cancer Consortium to participate in the NCI Cancer Prevention Fellowship Program, beginning with a Masters in Public Health from National University of Ireland, Dublin from Sept 2005-June 2006.  In July of 2006, Dr. Glynn moved to the NCI in Bethesda Maryland to begin her fellowship, where she worked in the Laboratory of Human Carcinogenesis under the mentorship of Dr. Stefan Ambs from September 2006-August 2009.  During her time in the Laboratory of Human Carcinogenesis, Dr. Glynn studied the role of inflammation pathways in estrogen receptor (ER) negative breast cancer progression using an approach which combines molecular epidemiology and basic laboratory science.  She discovered a novel role for NOS2 in ER negative and basal-like breast cancer progression.  Dr. Glynn also discovered a polymorphism in the SOD2 gene predicative of response to cyclophosphamide containing chemotherapeutic regimens in breast cancer cases, which is currently under development as a prognostic indicator. In 2009 Dr. Glynn received an NIH Fellows Award for Research Excellence for this work.  In September 2009 Dr. Glynn moved to the Radiation Biology Branch at NCI, to continue working with Dr. David Wink, with whom Dr. Glynn and Dr. Ambs had collaborated with on the previously described projects, in order to explore therapeutic avenues for their work. During this time Dr. Glynn was awarded a Keystone Symposia Scholarship for her work. In September 2010 Dr. Glynn was recruited by the Prostate Cancer Institute at NUI Galway as the Director of Laboratory Research.   Dr. Glynn continues to collaborate with colleagues in the NIH and was recently invited back to the NCI to present a paper at the Redox Biology Faculty's Symposium entitled ?Inflammation and Redox Biology in Cancer progression.?

Research Interests

Prostate Cancer Drug Development

Developing new therapeutics for the treatment of hormone-refractory prostate cancer, aimed at increasing patient survival and improving quality of life.  We are developing a programme of research aimed at testing novel compounds for activity against androgen resistant prostate cancer cells and ready them for assessment in clinical phase I trials. Additionally we will use molecular modelling approaches to identify novel therapeutic targets, and specifically develop new compounds against these.  

 

Molecular Determinants

One of the greatest limitations currently in the field of prostate cancer care, is the ability to predict those patients who after initial treatment of their primary disease, be it surgery or radiotherapy, will experience a recurrence.  There are several excellent prediction models which calculate risk of prostate cancer recurrence.  The Kattan and Partin models predict risk of recurrence post-radical prostatectomy, combining PSA scores, clinicopathological factors such as Gleason scores, seminal vesicle and nodal involvement, extra capsular extension, and pre-prostatectomy treatment.  However they don't address the biological factors which contribute to risk.  What are the specific molecular pathways which make one tumour more aggressive than the next, and can we identify a specific set of genes, which when expressed carry a high probability of tumour recurrence.  We plan to develop a 10-15 gene predictor of prostate cancer recurrence, which will also provide us with new molecular targets for systemic therapy to prevent prostate cancer recurrence in those at high risk, and treat patients with recurrent and metastatic disease. We hypothesize that tumours from prostate cancer patients who are at high risk of recurrence, have intrinsic biological differences to tumours from patients at low risk of recurrence.  By identifying those genes, proteins and pathways that are responsible for this increased risk, we will be able to better identify patients at risk, identify recurrence earlier, and provide us with molecular targets for therapeutic intervention.

Brachytherapy

Prostate cancer patients diagnosed with early stage localized prostate cancer have multiple treatment options including radical prostatectomy, external beam radiation (EBRT) and brachytherapy. Patients who choose brachytherapy for have excellent outcomes equivalent to patients undergoing radical prostatectomy (Arvold, 2011, J Urol). As these patients have many years to live (10-year survival 85-90%), and are likely to die with their disease not from it, treatment option decision making needs to take into account not only risk of recurrence/progression, but also risk of adverse effects of treatment that impact upon patient quality of life (QOL). All forms of treatment for localized prostate cancer come with their own inherent risks. Ferrar et al (2008, Int J Radiat Oncol Biol Phys) utilized a repeated measures analysis of variance of QOL measures to compare QOL issues after radical prostatectomy, 3D conformal radiotherapy and brachytherapy. Brachytherapy appears to have the least adverse impact on patient QOL of the three.  However adverse effects on urinary function, bowel function and sexual function are still observed particularly in the first 3 months post implantation. As these patients can expect to live with their disease for many years it is vital that we identify the factors that increase the risk of adverse events after a particular treatment modality, in this case brachytherapy, so that we can better match the patient to the appropriate treatment and also better understand what causes these adverse effects in patients.  We hypothesize that intrinsic phenotypic properties of an individual patient's prostate and inherited genetic polymorphisms predispose the patient to the development of adverse side-effects post brachytherapy. Our primary objective is to identify predictors and/or biomarkers for risk of adverse outcomes after brachytherapy, and also a biomarker for monitoring potential development of adverse side-effects long term (>1 year out)

Inflammation and Breast and Prostate Cancer
 
Chronic inflammation and infection are major mediators of cancer initiation and cancer progression.  Key mediators of inflammation-induced cancer include NFkB, reactive oxygen and nitrogen species, inflammatory cytokines, prostaglandins and specific microRNAs, which in turn exert their effects though changes in cell proliferation, apoptosis, cellular senescence, DNA mutation rates, DNA methylation, cell invasiveness and angiogenesis. Together these species present the ideal targets for early detection, diagnosis, prediction of outcome and also therapeutic targets. Nitric oxide (NO) the product of nitric oxide synthase 2 (NOS2) can influence tumour biology in various and sometimes dichotomous ways. Genetic ablation of NOS2 increases mammary tumour latency and inhibits lung tumour development in mouse models of cancer. These genetic findings demonstrate that NOS2 can have tumour promoting activities. However, NOS2 expression or other forms of NO exposure are not always tumour promoting, and there are many examples where exposure to NO either delayed or inhibited tumour growth and metastasis. Because the effects of NO are strictly concentration-dependent with high concentrations causing cytostasis and apoptosis, at least some of the observed differences are likely explained by a difference in levels of NO exposure.
 

Human Endogenous Retrovirus Activation

In recent years scientists have observed that several tumor types, including prostate cancer, show increased expression of human endogenous retrovirus (HERV) when compared to normal tissue. Why are these HERVs of interest? The HERVs originated from germ cell infections by exogenous retroviruses during the course of evolution and became incorporated into the human genome. These elements are widely dispersed throughout the genome and are estimated to comprise of greater than >8% of genomic material. Over 20 HERV families have been identified to date, the majority of which are defective due to mutations, deletions or termination signals within coding regions. The HERV-K family, evolutionarily the youngest HERV, is the only HERV family with complete open reading frames for all viral genes, and thus are the most likely to be biologically active and potentially pathogenic. Several questions need to be asked about HERV-K in prostate cancer. Is HERV-K activation a bystander effect in prostate cancer or is it linked to active prostate progression; can it distinguish indolent from aggressive disease? What is the major activator of HERV-K expression in prostate cancer? Does chronic inflammation in prostate tissues lead to the activation of HERV-K expression or does activation of HERV-K lead to tissue inflammation and subsequent carcinogenesis? Pockets of inflammation are often observed in prostate tissues that are not actually cancerous tissue but are thought to be associated with increased risk of prostate cancer.
 
 
Publications

Peer Reviewed Publications (25):

1.         Toner AP, McLaughlin F, Giles FJ, Sullivan FJ, Carleton L, Gorman A, Breen L, Dunne G, Lewis J, Glynn SA. EL102, a novel microtubule inhibitor with pre-clinical activity against prostate cancer. (Br J Cancer, E-pub ahead of print). Impact Factor (IF) = 5.0.

2.         Ridnour LA, Cheng RY, Switzer CH, Heinecke JL, Ambs S, Glynn S, Young HA, Trinchieri G, Wink DA. Molecular Pathways: Toll-like Receptors in the Tumor Microenvironment: Poor Prognosis or New Therapeutic Opportunity. Clin Cancer Res. 2013 Mar 15;19(6):1340-6. Impact Factor (IF) = 7.7

3.         Burke AJ, Giles FJ, Sullivan, FJ, Glynn SA. The Yin and Yang of nitric oxide in cancer progression. Carcinogenesis. 2013 Mar;34(3):503-12. IF = 5.7

4.         Mee B, Gaffney E, Glynn SA, Donatello S, Carroll P, Connolly E, Garrigle SM, Boyle T, Flannery D, Sullivan FJ, McCormick P, Griffin G, Muldoon C, Fay J, O'Grady T, Kay E, Eustace J, Burke L, Sheikh AA, Finn S, Flavin R, Giles FJ. Development and Progress of Ireland's Biobank Network: Ethical, Legal, and Social Implications (ELSI), Standardized Documentation, Sample and Data Release, and International Perspective. Biopreservation and Biobanking 2013 Feb 1st;11 (1), 3-11. IF = 1.3

5.         Hudson RS, Yi M, Esposito D, Glynn SA, Starks AM, Yang Y, Schetter AJ, Watkins SK, Hurwitz AA, Dorsey TH, Stephens RM, Croce CM, Ambs S. MicroRNA-106b-25 cluster expression is associated with early disease recurrence and targets caspase-7 and focal adhesion in human prostate cancer. Oncogene. 2012 Sep 17. doi: 10.1038/onc.2012.424.  IF = 6.3

6.         Switzer CH, Cheng RY, Ridnour LA, Glynn SA, Ambs S, Wink DA. Ets-1 is a transcriptional mediator of oncogenic nitric oxide signaling in estrogen receptor-negative breast cancer. Breast Cancer Res. 2012 Sep 12;14(5):R125. IF = 5.2

7.         Ridnour LA, Barasch KM, Windhausen AN, Dorsey TH, Lizardo MM, Yfantis HG, Lee DH, Switzer CH, Cheng RY, Heinecke JL, Brueggemann E, Hines HB, Khanna C, Glynn SA, Ambs S, Wink DA. Nitric Oxide Synthase and Breast Cancer: Role of TIMP-1 in NO-mediated Akt Activation. PLoS One. 2012;7(9):e44081. IF = 4.0

8.         Switzer CH, Glynn SA, Cheng RY, Ridnour LA, Green JE, Ambs S, Wink DA. S-Nitrosylation of EGFR and Src Activates an Oncogenic Signaling Network in Human Basal-Like Breast Cancer. Mol Cancer Res. 2012 Sep;10(9):1203-15. IF = 4.2

9.         Zhao J, Rycaj K, Geng S, Li M, Plummer JB, Yin B, Liu H, Xu X, Zhang Y, Yan Y, Glynn SA, Dorsey TH, Ambs S, Johanning GL, Gu L, Wang-Johanning F. Expression of Human Endogenous Retrovirus Type K Envelope Protein is a Novel Candidate Prognostic Marker for Human Breast Cancer. Genes Cancer. 2011 Sep;2(9):914-22. IF = New Journal

10.       Switzer CH, Cheng RY, Ridnour LA, Murray MC, Tazzari V, Sparatore A, Del Soldato P, Hines HB, Glynn SA, Ambs S, Wink DA. Dithiolethiones inhibit NF-κB activity via covalent modification in human estrogen receptor-negative breast cancer. Cancer Res. 2012 May 1;72(9):2394-404. IF = 7.8

11.       Switzer CH, Ridnour LA, Cheng R, Heinecke J, Burke A, Glynn S, Ambs S, Wink DA. S-Nitrosation Mediates Multiple Pathways That Lead to Tumor Progression in Estrogen Receptor-Negative Breast Cancer. For Immunopathol Dis Therap. 2012;3(2):117-124. IF = New Journal

12.       Wang-Johanning F, Rycaj K, Plummer JB, Li M, Yin B, Frerich K, Garza JG, Shen J, Lin K, Yan P, Glynn SA, Dorsey TH, Hunt KK, Ambs S, Johanning GL. Immunotherapeutic potential of anti-human endogenous retrovirus-K envelope protein antibodies in targeting breast tumors. J Natl Cancer Inst. 2012 Feb 8;104(3):189-210. IF = 13.7

13.       Switzer CH, Glynn SA, Ridnour LA, Cheng RY, Vitek MP, Ambs S, Wink DA. Nitric oxide and protein phosphatase 2A provide novel therapeutic opportunities in ER-negative breast cancer. Trends Pharmacol Sci. 2011 Sep 3. IF = 10.9

14.       Ambs S, Glynn SA. Candidate pathways linking inducible nitric oxide synthase to a basal-like transcription pattern and tumor progression in human breast cancer. Cell Cycle, 2011 Feb 15;10(4):619-24. IF 5.3

15.       Flores-Santana W, Salmon DJ, Donzelli S, Switzer CH, Basudhar D, Ridnour L, Cheng R, Glynn SA, Paolocci N, Fukuto JM, Miranda KM, Wink DA. The Specificity of Nitroxyl Chemistry Is Unique Among Nitrogen Oxides in Biological Systems. Antioxid Redox Signal. 2011 Mar 16. IF = 8.4

16.       Glynn SA, Prueitt RL, Ridnour LA, Boersma BJ, Dorsey TM, Wink DA, Goodman JE, Yfantis HG, Lee DH, Ambs S. COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer. BMC Cancer. 2010 Nov 15;10:626. IF = 3.0

17.       Glynn SA, Boersma BJ, Martin D, Howe TM, Ridnour LA, Wink DA, Yi M, Stephens RM, Yfantis HG and Ambs S. NOS2 predicts survival in estrogen receptor-negative breast cancer and is associated with a prognostic basal-like transcription pattern. J Clinical Investigation, 120, 3843-54. IF = 13.0

18.       Glynn SA, Boersma BJ, Howe TM, Edvardsen H, Geisler S, Goodman JE, Ridnour LA, Lonning PE, Børresen-Dale AL, Naume B, Kristensen VN, Chanock SJ, Wink DA, and Ambs S (2009) A mitochondrial targeting sequence polymorphism in the MnSOD gene predicts inferior survival in breast cancer patients treated with cyclophosphamide. Clinical Cancer Research, 15(12) 4165-73. IF= 7.7

19.       Glynn SA, O'Sullivan D, Eustace AJ, Clynes M, O'Donovan N. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, simvastatin, lovastatin and mevastatin inhibit proliferation and invasion of melanoma cells. BMC Cancer. 2008 Jan 16;8(1):9 IF = 3.0

20.       Dowling P, Maurya P, Meleady P, Glynn SA, Dowd AJ, Henry M, Clynes M. Purification and identification of a 7.6-kDa protein in media conditioned by superinvasive cancer cells. Anticancer Res. 2007 May-Jun;27(3A):1309-17. IF = 1.7

21.       Dowling P, Meleady P, Dowd A, Henry M, Glynn S, Clynes M. Proteomic analysis of isolated membrane fractions from superinvasive cancer cells. Biochim Biophys Acta. 2007 1774(1):93-101 IF = 3.6

22.       Glynn SA, Adams A, Gibson B, Cronin D, Harmey JH, Clynes M. (2006) Low adhesiveness coupled with high superinvasiveness in vitro predicts the in vivo metastatic potential of a mouse mammary adenocarcinoma cell line. Anticancer Res, 26(2A), 1001-1010. IF = 1.7

23.       Glynn SA, Gammell P, Heenan M, O'Connor R, Liang Y, Keenan J and Clynes M. (2004) A new superinvasive in vitro phenotype induced by selection of human breast carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin. Br J Cancer, 91, 1800-1807. IF = 5.0

24.       O'Driscoll L, Cronin D, Kennedy SM, Purcell R, Linehan R, Glynn S, Larkin A, Scanlon K, McDermott EW, Hill AD, O'Higgins NJ, Parkinson M, Clynes M. (2004) Expression and prognostic relevance of Mcl-1 in breast cancer. Anticancer Res, 24, 473-482. IF = 1.7

25.       O'Driscoll L, Linehan R, Kennedy SM, Cronin D, Purcell R, Glynn S, McDermott EW, Hill AD, O'Higgins NJ, Parkinson M, Clynes M. (2003) Lack of prognostic significance of survivin, survivin-deltaEx3, survivin-2B, galectin-3, bag-1, bax-alpha and MRP-1 mRNAs in breast cancer. Cancer Lett, 201, 225-236. IF = 4.2

 Scientific Meeting Abstracts ? Oral Presentation (5)

1.         Glynn SA, Switzer C, Howe TM, Ridnour LA, Yfantis HG, Ambs S and Wink DA. Joint expression of Nitric Oxide Synthase-2 and Cyclooxygenase-2 in Estrogen Receptor Negative Breast Cancer ? Acquisition of a Poor Prognosis Phenotype. Irish Association for Cancer Research, Radisson Hotel, Galway, Ireland. March 3rd to 5th 2010.

2.         Glynn SA, Switzer C, Howe TM, Ridnour LA, Yfantis HG, Ambs S and Wink DA. Joint expression of Nitric Oxide Synthase-2 and Cyclooxygenase-2 in Estrogen Receptor Negative Breast Cancer ? Acquisition of a Poor Prognosis Phenotype. Keystone Symposia on Cancer and Inflammation, Keystone, Colorado, USA. February 7th to 12th 2010.

3.         Glynn SA, Boersma BJ, Howe TM, Edvardsen H, Geisler S, Goodman JE, Ridnour LA, Lonning PE, Børresen-Dale AL, Kristensen VN, Chanock SJ, Wink DA, and Ambs S. A Mitochondrial Targeting Sequence Polymorphism in the MnSOD Gene Predicts Poor Response and Inferior Survival in Breast Cancer Patients Treated with Cyclophosphamide. NCI-CCR postdocs retreat, Hershey, Pennsylvania. March 18rd to 20th 2009.

4.         Glynn SA, Boersma BJ, Martin D, Howe TM, Ridnour L, Wink D, Stephens R, Yi M, Yfantis H, and Ambs S. High expression of iNOS is associated with a basal-like breast cancer phenotype and predicts poor survival in estrogen receptor negative breast cancer. NCI-CCR postdocs retreat, Clarion Hotel, Ocean City, Maryland. March 3rd to 5th 2008.

5.         Glynn SA, Boersma BJ, Martin D, Howe TM, Ridnour L, Wink D, Stephens R, Yi M, Yfantis H, and Ambs S. High expression of iNOS is associated with a basal-like breast cancer phenotype and predicts poor survival in estrogen receptor negative breast cancer. First International Conference on NO and Cancer, Paris, France. November 26th to 28th 2007.

 

Recent Abstracts in Published Conference Proceedings (2012-2013)

1.         Title: Introducing novel toluidine sulfonamide EL102, a potential chemotherapeutic in prostate cancer Author(s): Toner, A.; Giles, F. J.; Sullivan, F. J.; Walsh, K., Durkan, G., Rogers, E., Lewis, JD, Glynn, SA. Source: BJU INTERNATIONAL  Volume: 111   Special Issue: SI   Supplement: 3   Pages: 61-61   Meeting Abstract: P105   Published: JUN 2013

2.         Title: Cellular fate assessment in triple negative breast cancer (TNBC) predict chemoresponse and patient outcome Author(s): O'Reilly, Elma A.; Sharma, Shiva; Klinger, Rut; et al. Source: IRISH JOURNAL OF MEDICAL SCIENCE  Volume: 182   Supplement: 2   Pages: S31-S32   Published: MAR 2013

3.         Title: Prostate cancer inhibitory activity of a novel dual inhibitor, EL102, in combination with docetaxel, and its effects on MDR1-mediated drug resistance in vitro. Author(s): Glynn, Sharon A.; Toner, Aidan; Lewis, Joe; et al.Source: JOURNAL OF CLINICAL ONCOLOGY  Volume: 30   Issue: 15   Supplement: S   Meeting Abstract: e15126   Published: MAY 20 2012

4.         Title: EL102: A novel dual inhibitor which demonstrates additive prostate cancer inhibitory activity in combination with docetaxel in vitro and in mouse models. Author(s): Aidan Toner, Fiona McLaughlin, Jill McMahon, Francis J Giles, Frank Sullivan, Laura Breen, Martin Clynes, Joe D Lewis, Sharon A Glynn. Source: CANCER RESEARCH Volume: 72 Issue: 4 Supplement Meeting Absstract: B18  Published: FEBRUARY 6 2012

5.         Title: Human endogenous retrovirus activation in prostate cancer: Association with disease progression. Author(s): Ronan Downey, Amy Burke, Francis J Giles, Frank Sullivan, Feng Wang-Johanning, Blanaid Mee, Eoin Gaffney, Sharon A Glynn. Source: CANCER RESEARCH Volume: 72 Issue: 4 Supplement Meeting Absstract: A62  Published: FEBRUARY 6 2012

 

Graduate Students
Carol Johnson

Carol is originally from Ballinasloe and studied pharmacology in University College Dublin from 2005 - 2009. After completing a Bachelor of Science degree she chose to undertake a taught Masters degree in Neuropharmacology in NUI Galway to expand and strengthen her laboratory skills and techniques. The courses which she completed equipped her with essential skills suitable for transferring across various scientific disciplines. From here she applied for a PhD position in prostate cancer research within the Prostate Cancer Institute (PCI) and was successful with her application.

She started her research with the PCI in January 2011. Her main project aims are to investigate the role of inflammatory pathways in the survival and growth mechanisms involved in cancer progression and the development of hormonal independent prostate cancer. After completion of a PhD her ultimate career goal is to become a lecturer and research team leader, after sufficient post doctoral experience.
 
Aidan Toner

Aidan is a native of Corrandulla, Co. Galway. He obtained his BSc. (Hons) in Biochemistry at NUI, Galway in 2007. The following year he completed an internship at Duke University Medical Center, North Carolina, researching novel therapies in prostate cancer. This research identified a known transcription factor KLF5 as potential therapeutic target in specific forms of prostate cancer. It was through this work that Aidan obtained his MSc. (Research) from NUI, Galway.

He began research for his PhD study at the Prostate Cancer Institute in January 2011. He is exploring key mechanisms of epithelial-mesenchymal transition (EMT) as a major driver of prostate cancer progression, namely the transition from non-aggressive localised prostate cancer to a more aggressive invasive phenotype, leading to metastatic disease. Following completion of his doctoral study, Aidan hopes to ultimately start his own research group with a continued focus of developing novel cancer therapies.

Honours & Awards

March 2010:                         Prostate Cancer Research Award, (€750K over 4 years), at National University of Ireland Galway.

February 2010:                    Awarded Keystone Symposia Scholarship 2010.

June 2009:                            NCI press release: Genetic Variant Associated with Resistance to Chemotherapy Drug in Women with Breast Cancer. http://www.cancer.gov/newscenter/pressreleases/BreastSNPChemoAmbs

May 2009:                             Fellows Award for Research Excellence 2009, Center for Cancer Research, National Cancer Institute.

2005 - 2009:                         All-Ireland Cancer Consortium sponsored NCI Cancer Prevention Fellowship.

July-Aug 2003:                     Travel Award from Health Research Board of Ireland to attend the Principles and Practices of Cancer Prevention and Control Diploma course, at NCI, Bethesda, Maryland, USA.

1997-1998:                           Forbairt Partnership Scholars Programme, funded through the Irish American Partnership, providing £10,000 over 2 years.

Summer 1995:                     Welcome Trust Summer Studentship in University College Galway (Dr. Denis Headon).